(bue piv' a kane hye'' droe klor' ide).
2-Piperidinecarboxamide, 1-butyl-N-(2,6-dimethylphenyl)-, monohydrochloride, monohydrate, (±)-.
(±)-1-Butyl-2¢,6¢-pipecoloxylidide monohydrochloride, monohydrate [73360-54-0].
Anhydrous 324.90 [18010-40-7].
» Bupivacaine Hydrochloride contains not less than 98.5 percent and not more than 101.5 percent of C18H28N2O·HCl, calculated on the anhydrous basis.
Packaging and storage Preserve in well-closed containers.
USP Reference standards 11
A: Infrared Absorption 197S
Solution Dissolve about 230 mg in 15 mL of water in a separator, add 1 mL of 6 N ammonium hydroxide, and extract with three 30-mL portions of chloroform. Evaporate the chloroform at room temperature with the aid of a stream of nitrogen, and dry the residue in vacuum. Add 2 mL of chloroform to the residue, and dissolve.
B: Ultraviolet Absorption 197U
Solution: 500 µg per mL.
Medium: 0.1 N hydrochloric acid.
Absorptivities at 271 nm, calculated on the anhydrous basis, do not differ by more than 3.0%.
C: Dissolve about 50 mg in 10 mL of water in a small separator, render alkaline with 6 N ammonium hydroxide, and extract with 10 mL of ether: the aqueous layer meets the requirements of the tests for Chloride 191.
pH 791: between 4.5 and 6.0, in a solution (1 in 100).
Water, Method I 921: between 4.0% and 6.0%.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: not more than 0.001%.
Limit of residual solvents
Alcohol standard solution Pipet 2 mL of dehydrated alcohol into a 100-mL volumetric flask, dilute with water to volume, and mix. Transfer 2.0 mL of this solution to a 50-mL volumetric flask, dilute with water to volume, and mix. The resulting solution contains 0.08% of alcohol.
Isopropyl alcohol standard solution Pipet 2 mL of isopropyl alcohol into a 1000-mL volumetric flask, dilute with water to volume, and mix. Transfer 2.0 mL of this solution to a 100-mL volumetric flask, dilute with water to volume, and mix. The resulting solution contains 0.004% of isopropyl alcohol.
Test solution Transfer 1.0 g of Bupivacaine Hydrochloride, accurately weighed, to a 25-mL volumetric flask, dilute with water to volume, and mix.
Chromatographic system Under typical conditions, the instrument is equipped with a flame-ionization detector and a 4-mm × 2-m column that contains packing S3. The carrier gas is nitrogen, flowing at a rate of about 40 mL per minute. The column temperature is maintained at about 175, the injection port temperature is maintained at about 200, and the detector temperature is maintained at about 280.
Procedure Inject equal volumes (about 5 µL) of the Test solution, the Alcohol standard solution, and the Isopropyl alcohol standard solution successively into the gas chromatograph. Measure the responses of the alcohol peak and the isopropyl alcohol peak in each chromatogram. Determine the percentage of alcohol taken by the formula:
2(rU / rS)and determine the percentage of isopropyl alcohol taken by the formula:
0.1(rU / rS)in which rU and rS are the responses of the respective analytes in the Test solution and of the corresponding analytes in the Alcohol standard solution and the Isopropyl alcohol standard solution, respectively. The sum of the content of alcohol and the content of isopropyl alcohol does not exceed 2%.
Adsorbent: 0.25-mm layer of chromatographic silica gel mixture.
Solvent: a mixture of chloroform and isopropylamine (99:1).
Test solution Dissolve a suitable quantity of Bupivacaine Hydrochloride in Solvent to obtain a solution containing 20.0 mg per mL.
Standard solution Dissolve a suitable quantity of USP Bupivacaine Hydrochloride RS, accurately weighed, in Solvent to obtain a solution containing 20.0 mg per mL.
Diluted standard solution Quantitatively dilute a portion of the Standard solution in Solvent to obtain a solution having a concentration of 100 µg per mL.
Developing solvent system: a mixture of hexanes and isopropylamine (97:3).
Procedure Apply separate 10-µL portions of the Test Solution, the Standard solution, and the Diluted standard solution on the starting line of suitable thin-layer chromatographic plate as directed for Thin-Layer Chromatography under Chromatography 621. Develop the chromatogram in a suitable chamber until the solvent has moved about three-fourths of the length of the plate. Remove the plate from the chamber, mark the solvent front, and dry it in warm air. Place the plate in a closed chamber with a dish containing 1 g of iodine in a shallow layer, and allow to remain for about 5 minutes. Remove the plate from the chamber, spray it with 7 N sulfuric acid, and examine the chromatogram: the RF value of the principal spot from the Test solution corresponds to that of the Standard solution, and the estimated size and intensity of any other spot obtained from the Test solution does not exceed that of the principal spot obtained from the Diluted standard solution (0.5%); and the total of the estimated sizes and intensities of all of the other spots obtained from the Test solution does not exceed four times that of the principal spot obtained from the Diluted standard solution (2.0%).
Assay Transfer about 600 mg of Bupivacaine Hydrochloride, accurately weighed, to a 250-mL conical flask, and dissolve in 20 mL of glacial acetic acid. Add 10 mL of mercuric acetate TS and 3 drops of crystal violet TS, and titrate with 0.1 N perchloric acid VS to a green endpoint. Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 32.49 mg of C18H28N2O·HCl.
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USP35NF30 Page 2399Pharmacopeial Forum: Volume No. 34(1) Page 75